ANO1

Last updated

ANO1
Identifiers
Aliases ANO1 , DOG1, ORAOV2, TAOS2, TMEM16A, anoctamin 1
External IDs OMIM: 610108 MGI: 2142149 HomoloGene: 75079 GeneCards: ANO1
Orthologs
SpeciesHumanMouse
Entrez

55107

101772

Ensembl

ENSG00000131620

ENSMUSG00000031075

UniProt

Q5XXA6

Q8BHY3

RefSeq (mRNA)

NM_001242349
NM_178642

RefSeq (protein)

NP_001229278
NP_848757

Location (UCSC) Chr 11: 69.99 – 70.19 Mb Chr 7: 144.14 – 144.31 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Anoctamin-1 (ANO1), also known as Transmembrane member 16A (TMEM16A), is a protein that, in humans, is encoded by the ANO1 gene. [5] [6] Anoctamin-1 is a voltage-gated calcium-activated anion channel, which acts as a chloride channel [7] and a bicarbonate channel. [8] additionally Anoctamin-1 is apical iodide channel. It is expressed in smooth muscle, epithelial cells, [9] vomeronasal neurons, [10] olfactory sustentacular cells, [11] and is highly expressed in interstitial cells of Cajal (ICC) throughout the gastrointestinal tract. [12]

Contents

Function

ANO1 is a transmembrane protein that functions as a calcium-activated chloride channel. [13] Ca2+, Sr2+, and Ba2+ activate the channel. [14]

Structure

No atomic resolution structure of this channel has yet been obtained. [15] However, biochemical evidence suggests that the channel assembles as a dimer of two ANO1 polypeptide subunits. [16] [17] From hydropathy plotting, each subunit is thought to encode a molecule with eight transmembrane domains, with a reentrant loop between the fifth and sixth transmembrane domains. The reentrant loop is thought to be a P loop-like structure responsible for the ion selectivity of the protein. [18]

Clinical significance

In mice, the functional expression of the ANO1 channel is essential to life, as its absence leads to a premature death due to respiratory collapse. [19]

ANO1 is expressed in the gastrointestinal tract and is highly expressed in interstitial cells of Cajal, where it plays an important role in pacemaker activity, neurotransduction of enteric motor neurotransmitters and regulation of gastrointestinal motility. [12] [20] [9] ANO1 blockers like niflumic acid have been shown to block slow waves, which produce phasic contractions and the major patterns of gastrointestinal motility, such as peristalsis and segmentation. [12] [20] ANO1-knockout mice fail to produce slow waves altogether. [12] [20] Carbachol has been shown to markedly activate the channel due to its effect on release of Ca2+ from intracellular stores. [12] [20] ANO1 activation is necessary for normal function of ICC and generation of normal patterns of activity in smooth muscles of the gastrointestinal tract. [12] [20]

Its overexpression was reported in esophageal squamous cell carcinoma and breast cancer progression. [21] [22]

Related Research Articles

<span class="mw-page-title-main">Ion channel</span> Pore-forming membrane protein

Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of ions across the cell membrane, controlling the flow of ions across secretory and epithelial cells, and regulating cell volume. Ion channels are present in the membranes of all cells. Ion channels are one of the two classes of ionophoric proteins, the other being ion transporters.

Calcium release-activated channels (CRAC) are specialized plasma membrane Ca2+ ion channels. When calcium ions (Ca2+) are depleted from the endoplasmic reticulum (a major store of Ca2+) of mammalian cells, the CRAC channel is activated to slowly replenish the level of calcium in the endoplasmic reticulum. The Ca2+ Release-activated Ca2+ (CRAC) Channel (CRAC-C) Family (TC# 1.A.52) is a member of the Cation Diffusion Facilitator (CDF) Superfamily. These proteins typically have between 4 and 6 transmembrane α-helical spanners (TMSs). The 4 TMS CRAC channels arose by loss of 2TMSs from 6TMS CDF carriers, an example of 'reverse' evolution'.

<span class="mw-page-title-main">Voltage-gated ion channel</span> Type of ion channel transmembrane protein

Voltage-gated ion channels are a class of transmembrane proteins that form ion channels that are activated by changes in the electrical membrane potential near the channel. The membrane potential alters the conformation of the channel proteins, regulating their opening and closing. Cell membranes are generally impermeable to ions, thus they must diffuse through the membrane through transmembrane protein channels. They have a crucial role in excitable cells such as neuronal and muscle tissues, allowing a rapid and co-ordinated depolarization in response to triggering voltage change. Found along the axon and at the synapse, voltage-gated ion channels directionally propagate electrical signals. Voltage-gated ion-channels are usually ion-specific, and channels specific to sodium (Na+), potassium (K+), calcium (Ca2+), and chloride (Cl−) ions have been identified. The opening and closing of the channels are triggered by changing ion concentration, and hence charge gradient, between the sides of the cell membrane.

<span class="mw-page-title-main">Chloride channel</span> Class of transport proteins

Chloride channels are a superfamily of poorly understood ion channels specific for chloride. These channels may conduct many different ions, but are named for chloride because its concentration in vivo is much higher than other anions. Several families of voltage-gated channels and ligand-gated channels have been characterized in humans.

<span class="mw-page-title-main">G protein-gated ion channel</span>

G protein-gated ion channels are a family of transmembrane ion channels in neurons and atrial myocytes that are directly gated by G proteins.

<span class="mw-page-title-main">Interstitial cell of Cajal</span>

Interstitial cells of Cajal (ICC) are interstitial cells found in the gastrointestinal tract. There are different types of ICC with different functions. ICC and another type of interstitial cell, known as platelet-derived growth factor receptor alpha (PDGFRα) cells, are electrically coupled to smooth muscle cells via gap junctions, that work together as an SIP functional syncytium. Myenteric interstitial cells of Cajal (ICC-MY) serve as pacemaker cells that generate the bioelectrical events known as slow waves. Slow waves conduct to smooth muscle cells and cause phasic contractions.

<span class="mw-page-title-main">TRPV6</span> Protein-coding gene in the species Homo sapiens

TRPV6 is a membrane calcium (Ca2+) channel protein which is particularly involved in the first step in Ca2+absorption in the intestine.

<span class="mw-page-title-main">TRPV5</span> Protein-coding gene in the species Homo sapiens

Transient receptor potential cation channel subfamily V member 5 is a calcium channel protein that in humans is encoded by the TRPV5 gene.

<span class="mw-page-title-main">STIM1</span> Protein-coding gene in the species Homo sapiens

Stromal interaction molecule 1 is a protein that in humans is encoded by the STIM1 gene. STIM1 has a single transmembrane domain, and is localized to the endoplasmic reticulum, and to a lesser extent to the plasma membrane.

<span class="mw-page-title-main">Calcium-activated potassium channel subunit alpha-1</span> Voltage-gated potassium channel protein

Calcium-activated potassium channel subunit alpha-1 also known as large conductance calcium-activated potassium channel, subfamily M, alpha member 1 (KCa1.1), or BK channel alpha subunit, is a voltage gated potassium channel encoded by the KCNMA1 gene and characterized by their large conductance of potassium ions (K+) through cell membranes.

<span class="mw-page-title-main">Bestrophin 1</span> Protein-coding gene in the species Homo sapiens

Bestrophin-1 (Best1) is a protein that, in humans, is encoded by the BEST1 gene.

<span class="mw-page-title-main">CLCA1</span> Protein-coding gene in the species Homo sapiens

Chloride channel accessory 1 is a protein that in humans is encoded by the CLCA1 gene.

<span class="mw-page-title-main">WNK4</span> Protein-coding gene in the species Homo sapiens

Serine/threonine protein kinase WNK4 also known as WNK lysine deficient protein kinase 4 or WNK4, is an enzyme that in humans is encoded by the WNK4 gene. Missense mutations cause a genetic form of pseudohypoaldosteronism type 2, also called Gordon syndrome.

<span class="mw-page-title-main">CLCA2</span> Protein-coding gene in the species Homo sapiens

Chloride channel accessory 2 is a protein that in humans is encoded by the CLCA2 gene.

<span class="mw-page-title-main">KCNMB2</span> Protein-coding gene in the species Homo sapiens

Calcium-activated potassium channel subunit beta-2 is a protein that in humans is encoded by the KCNMB2 gene.

<span class="mw-page-title-main">CLCA3</span> Pseudogene in the species Homo sapiens

Chloride channel accessory 3, also known as CLCA3, is a protein which in humans is encoded by the CLCA3P pseudogene. The protein encoded by this gene is a chloride channel. According to the HGNC, this protein is not expressed in humans but is in certain other species such as mouse. However, some conflicting reports state that human cells produce and glycosylate this protein.

<span class="mw-page-title-main">CLCA4</span> Protein-coding gene in the species Homo sapiens

Chloride channel accessory 4, also known as CLCA4, is a protein which in humans CLCA4 gene. The protein encoded by this gene is a chloride channel. Protein structure prediction methods suggest the N-terminal region of CLCA4 protein is a zinc metalloprotease, and the protein is not an ion channel per se.

ANO3 is a gene that in humans is located on chromosome 11 and encodes the protein anoctamin 3. It belongs to a family of genes (ANO1–ANO10) that appear to encode calcium-activated chloride channels.

<span class="mw-page-title-main">Calcium-dependent chloride channel</span> Group of transport proteins

The Calcium-Dependent Chloride Channel (Ca-ClC) proteins (or calcium-activated chloride channels, are heterogeneous groups of ligand-gated ion channels for chloride that have been identified in many epithelial and endothelial cell types as well as in smooth muscle cells. They include proteins from several structurally different families: chloride channel accessory, bestrophin, and calcium-dependent chloride channel anoctamin channels ANO1 is highly expressed in human gastrointestinal interstitial cells of Cajal, which are proteins which serve as intestinal pacemakers for peristalsis. In addition to their role as chloride channels some CLCA proteins function as adhesion molecules and may also have roles as tumour suppressors. These eukaryotic proteins are "required for normal electrolyte and fluid secretion, olfactory perception, and neuronal and smooth muscle excitability" in animals. Members of the Ca-CIC family are generally 600 to 1000 amino acyl residues in length and exhibit 7 to 10 transmembrane segments.

<span class="mw-page-title-main">ANO5</span> Protein-coding gene in the species Homo sapiens

Anoctamin 5 (ANO5) is a protein that in humans is encoded by the ANO5 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000131620 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000031075 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ "Entrez Gene: anoctamin 1, calcium activated chloride channel".
  6. ↑ Katoh M, Katoh M (June 2003). "FLJ10261 gene, located within the CCND1-EMS1 locus on human chromosome 11q13, encodes the eight-transmembrane protein homologous to C12orf3, C11orf25 and FLJ34272 gene products". International Journal of Oncology. 22 (6): 1375–81. doi:10.3892/ijo.22.6.1375. PMID   12739008.
  7. ↑ Yang YD, Cho H, Koo JY, Tak MH, Cho Y, Shim WS, et al. (October 2008). "TMEM16A confers receptor-activated calcium-dependent chloride conductance". Nature. 455 (7217): 1210–5. Bibcode:2008Natur.455.1210Y. doi:10.1038/nature07313. PMID   18724360. S2CID   205214858.
  8. ↑ Jung J, Nam JH, Park HW, Oh U, Yoon JH, Lee MG (January 2013). "Dynamic modulation of ANO1/TMEM16A HCO3(-) permeability by Ca2+/calmodulin". Proceedings of the National Academy of Sciences of the United States of America. 110 (1): 360–5. Bibcode:2013PNAS..110..360J. doi: 10.1073/pnas.1211594110 . PMC   3538232 . PMID   23248295.
  9. 1 2 Pedemonte N, Galietta LJ (April 2014). "Structure and function of TMEM16 proteins (anoctamins)". Physiological Reviews. 94 (2): 419–59. doi:10.1152/physrev.00039.2011. PMID   24692353.
  10. ↑ Amjad A, Hernandez-Clavijo A, Pifferi S, Maurya DK, Boccaccio A, Franzot J, et al. (April 2015). "Conditional knockout of TMEM16A/anoctamin1 abolishes the calcium-activated chloride current in mouse vomeronasal sensory neurons". The Journal of General Physiology. 145 (4): 285–301. doi:10.1085/jgp.201411348. PMC   4380210 . PMID   25779870.
  11. ↑ Henriques T, Agostinelli E, Hernandez-Clavijo A, Maurya DK, Rock JR, Harfe BD, Menini A, Pifferi S (1 July 2019). "TMEM16A calcium-activated chloride currents in supporting cells of the mouse olfactory epithelium". The Journal of General Physiology. 151 (7): 954–966. doi:10.1085/jgp.201812310. ISSN   0022-1295. PMC   6605691 . PMID   31048412.
  12. 1 2 3 4 5 6 Sanders KM, Zhu MH, Britton F, Koh SD, Ward SM (February 2012). "Anoctamins and gastrointestinal smooth muscle excitability". Experimental Physiology. 97 (2): 200–6. doi:10.1113/expphysiol.2011.058248. PMC   3272164 . PMID   22002868.
  13. ↑ Kunzelmann K, Tian Y, Martins JR, Faria D, Kongsuphol P, Ousingsawat J, et al. (August 2011). "Anoctamins". Pflügers Archiv. 462 (2): 195–208. doi:10.1007/s00424-011-0975-9. PMID   21607626. S2CID   263991796.
  14. ↑ Ni YL, Kuan AS, Chen TY (2014). "Activation and inhibition of TMEM16A calcium-activated chloride channels". PLOS ONE. 9 (1): e86734. Bibcode:2014PLoSO...986734N. doi: 10.1371/journal.pone.0086734 . PMC   3906059 . PMID   24489780.
  15. ↑ Pfam PF04547; PDB search for PF04547 [ permanent dead link ]
  16. ↑ Fallah G, Römer T, Detro-Dassen S, Braam U, Markwardt F, Schmalzing G (February 2011). "TMEM16A(a)/anoctamin-1 shares a homodimeric architecture with CLC chloride channels". Molecular & Cellular Proteomics. 10 (2): S1–S11. doi: 10.1074/mcp.M110.004697 . PMC   3033684 . PMID   20974900.
  17. ↑ Sheridan JT, Worthington EN, Yu K, Gabriel SE, Hartzell HC, Tarran R (January 2011). "Characterization of the oligomeric structure of the Ca(2+)-activated Cl- channel Ano1/TMEM16A". The Journal of Biological Chemistry. 286 (2): 1381–8. doi: 10.1074/jbc.M110.174847 . PMC   3020746 . PMID   21056985.
  18. ↑ Xiao Q, Yu K, Perez-Cornejo P, Cui Y, Arreola J, Hartzell HC (May 2011). "Voltage- and calcium-dependent gating of TMEM16A/Ano1 chloride channels are physically coupled by the first intracellular loop". Proceedings of the National Academy of Sciences of the United States of America. 108 (21): 8891–6. Bibcode:2011PNAS..108.8891X. doi: 10.1073/pnas.1102147108 . PMC   3102354 . PMID   21555582.
  19. ↑ Rock JR, O'Neal WK, Gabriel SE, Randell SH, Harfe BD, Boucher RC, Grubb BR (May 2009). "Transmembrane protein 16A (TMEM16A) is a Ca2+-regulated Cl- secretory channel in mouse airways". The Journal of Biological Chemistry. 284 (22): 14875–80. doi: 10.1074/jbc.C109.000869 . PMC   2685669 . PMID   19363029.
  20. 1 2 3 4 5 Zhu MH, Sung IK, Zheng H, Sung TS, Britton FC, O'Driscoll K, et al. (September 2011). "Muscarinic activation of Ca2+-activated Cl- current in interstitial cells of Cajal". The Journal of Physiology. 589 (Pt 18): 4565–82. doi:10.1113/jphysiol.2011.211094. PMC   3208225 . PMID   21768263.
  21. ↑ Kashyap MK, Marimuthu A, Kishore CJ, Peri S, Keerthikumar S, Prasad TS, et al. (January 2009). "Genomewide mRNA profiling of esophageal squamous cell carcinoma for identification of cancer biomarkers". Cancer Biology & Therapy. 8 (1): 36–46. doi: 10.4161/cbt.8.1.7090 . PMID   18981721.
  22. ↑ Britschgi A, Bill A, Brinkhaus H, Rothwell C, Clay I, Duss S, et al. (March 2013). "Calcium-activated chloride channel ANO1 promotes breast cancer progression by activating EGFR and CAMK signaling". Proceedings of the National Academy of Sciences of the United States of America. 110 (11): E1026-34. doi: 10.1073/pnas.1217072110 . PMC   3600458 . PMID   23431153.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.